This proposal requests support for a program of research to evaluate the role of choline availability in the control of brain acetylcholine synthesis. This research will be applied to the study of cholinergic mechanisms including various types of behavior (e.g., locomoter activity), to the modulation of effects of drugs that may influence cholinergic transmission (e.g., physostigmine; phenothiazines), and to the treatment of some human diseases that may also involve cholinergic synapses (e.g., tardive dyskinesia; Huntington's Disease). In preliminary experiments we have noted that choline, administered orally or by injection, increases brain acetylcholine levels, probably by accelerating the synthesis of the neurotransmitter. Projected studies will: 1) characterize further the choline-induced elevation in brain acetylcholine and relate it to acetylcholine synthesis; 2) determine whether administration of natural or pharmacologic precursors of choline (e.g., lecithin; dimethylaminoethanol) also elevates brain acetylcholine levels; 3) determine whether the choline-induced increases in brain acetylcholine levels are accompanied by increased release of the neurotransmitter; 4) study the physiology and pharmacology of central and peripheral cholinergic neurons and their involvement in various behavioral mechanisms, by examining the consequences of giving choline (alone or with drugs) to experimental animals; 5) study the interactions of central cholinergic and monoaminergic neurons; and, 6) explore the effectiveness of choline therapy (given alone or with other drugs) in behavioral and neurological disorders.